Project Summary The goal of the Boston Children's Hospital CHRCDA Program is to develop pediatrician physician-scientists who are performing world-class research that will improve health care for children in this country and around the world. Our Scholars will be performing laboratory-based basic and translational research under the mentorship of outstanding scientists at Children's Hospital and other Harvard Associated Hospitals and Harvard Medical School. Our program has been established to ensure the development of independent scientists. In this proposal we describe a program that includes intensive mentoring, a comprehensive didactic program, and a program to ensure the scientific development of Scholars. Programmatic oversight will be provided by an External Site Visit Committee and an Internal Steering Committee. Plans are in place for programmatic self-evaluation and for review of Scholar Progress. We propose to continue the funding of three Scholar positions. Scholars will be funded for a minimum of two years, with further funding contingent on progress and the overall pool of Scholar candidates. Scholars will be faculty members most often at the rank of Instructor, but Assistant Professors who are early in the development of their independent careers will also be eligible to apply. Scholars will be considered at any point from the beginning of their Instructorship to the point where they are considered to be two years away from submitting their first R-level NIH grant or equivalent, though no more than four years beyond the end of fellowship training. Scholars will work in a broad range of scientific investigations. Past and present Scholars have worked in areas such as the mechanism of nuclear reprogramming, structural biology of malaria antigens, immune response to tumors, cancer therapeutics, molecular bases for immunodeficiency, host-microbiome interactions, lung and intestinal stem cells, molecular pathology of streptococcal infection, and disorders of sexual differentiation. These investigations will elucidate fundamental molecular mechanisms and will lead to the development of new therapeutic modalities in all areas of pediatric disease, including hematology/oncology, endocrinology, nephrology, infectious disease, immunology, pulmonology and neurology. !